足细胞分子nephrin在高血压大鼠肾脏的表达及作用

目的探讨足细胞分子nephrin在自发性高血压大鼠（SHR）肾脏的表达及作用。方法监测不同时期SHR与京都大鼠（wistar-kyotorats,WKY）尾动脉收缩压（SBP）、尿β2-微球蛋白（β2-MG）、尿素氮（BUN）、血肌酐（SCr）水平;免疫组化、RT-PCR方法检测nephrin蛋白及mRNA的表达,观察肾脏的病理改变。结果与WKY组相比,SHR组SBP、β2-MG、BUN、SCr升高,nephrin蛋白及mRNA表达量下降,且nephrin含量与尿β2-MG呈负相关。SHR组肾脏发生病理改变。结论足细胞分子nephrin在SHR肾小球表达减少,可能是导致足细胞裂隙膜损伤,引起尿β2-MG排泄水平增加,肾功能受损,肾脏病理改变的基础。     

细胞间黏附分子-1在自发性高血压大鼠肾损害作用的研究

目的：研究细胞间黏附分子-1（ICAM-1）在自发性高血压大鼠（SHR）肾组织的表达及其与肾损害的关系。方法：以同龄雄性正常血压大鼠（WKY）和SHR为研究对象,分别于10周龄和28周龄检测两种大鼠尾动脉压、24h尿蛋白定量、肾功能等;留取肾组织行HE染色、免疫组织化学及RT-PCR法检测ICAM-1蛋白及mRNA表达情况,并作分析。结果：与同龄WKY大鼠比较,SHR尾动脉压和24h尿蛋白定量明显增高（P〈0.05和P〈0.05）;与12周龄SHR比较,28周龄SHR尾动脉压和24h尿蛋白定量明显增加（P〈0.05和P〈0.05）。SHR组肾组织ICAM-1蛋白及mRNA表达较同龄WKY增强（P〈0.05）,28周龄SHR较10周龄SHR表达增强（P〈0.05）,ICAM-1表达与24h尿蛋白定量呈正相关（P〈0.05）。结论：SHR出现蛋白尿时,肾组织ICAM-1表达增强,炎症参与了高血压肾损害的发生。     

高盐饮食对自发性高血压大鼠肾髓质环氧化酶2表达的影响

目的观察自发性高血压大鼠（SHR）肾髓质环氧化酶2（COX2）的表达以及不同盐负荷状态下COX2的变化。方法6周龄SHR大鼠及其对照Wistar-Kyoto（WKY）大鼠各12只，随机分为低盐组和高盐组（WKY-LS组，WKY-HS组，SHR-LS组，SHR-HS组），分别给予高盐（含8％NaCl）或低盐（含O．04％NaCl）饮食3d。观察基础状态及不同盐负荷前后大鼠尾动脉血压、24h尿量（UV）、尿钠（UNa）以及COX2代谢物6k．PGFlα排泄情况。应用免疫组化和Western印迹的方法检测肾髓质COX2蛋白表达。结果给予不同盐负荷3d后，SHR-Hs组血压显著升高[（12．59±5．13）比（11．94±3．76）mmHg，P〈0．05]。基础状态及不同盐负荷状态下，SHR大鼠24hUV、UNa排泄与WKY大鼠相比均显著下降（P均〈O．05）。与各自基础状态相比，低盐饮食后两种大鼠的UV和UNa排泄显著降低；高盐饮食后则显著增加（P均〈O．05）。SHR和WKY大鼠尿COX2代谢物6k-PGFlα的排泄对盐负荷的反应也类似，高盐组均较低盐组显著增加（P〈0．05），但同样盐负荷状态下两组之间差异无统计学意义。基础状态下及低盐饮食SHR与WKY大鼠肾髓质COX2表达差异无统计学意义；给予高盐饮食后WKY大鼠肾髓质COX2表达增加2．06倍，SHR大鼠增加1．87倍，但两种大鼠之间差异无统计学意义。结论SHR大鼠肾脏水盐排泄功能受损，高盐饮食后血压进一步升高，水钠潴留，同时伴有肾髓质COX2表达升高，但不同盐负荷对SHR大鼠肾髓质COX2表达的影响与WKY大鼠相同。提示肾髓质COX2参与了水盐代谢的调节，且在SHR大鼠中表达正常，但并非该动物模型高血压形成及水钠潴留的关键因素。     

Serum Cystatin C and β2-Microglobulin as Markers of Glomerular Filtration Rate

Continuous efforts have been made to find out precise and simple method for determination of glomerular filtration rate (GFR). Cystatin C (cysteine proteinase inhibitor = CyC) is a low molecular weight (LMW) protein which is produced constantly by all nucleated cells independently of different pathological conditions and eliminated from the blood exclusively by glomeruli. So, CyC closely reflects the GFR. In the present study 75 patients aged between 18 and 74 (44.3 ± 12.2) years were analyzed, with the aim to compare the reciprocal values of serum level of LMW proteins CyC and β₂-microglobulin (β₂-MG) with creatinine clearance (Ccr) as a measure of GFR. Patients were divided into groups according to sex, age (<60; >60 years) and renal diseases: patients with glomerulonephritis (GN) with and without nephrotic proteinuria, pyelonephritis (PyN), and renal transplant (Tx). High correlation between Ccr and 1/CyC (r = 0.81; p<0.01) and Ccr and 1/β₂-MG (r = 0.80; p<0.01) in all examined patients was found. There was significant correlation between Ccr and 1/CyC (0.82 vs. 0.79) and Ccr and 1/β₂-MG (0.85 vs. 0.76) in men as well in women, and also in two groups of patients formed according to the age (0.82 vs. 0.77; p<0.01; 0.80 vs. 0.81; p<0.01), without any statistical significant difference between the groups. In studied groups with different renal diseases, there were no differences in correlation coefficients between Ccr and 1/CyC and Ccr and 1/β₂-MG (p1 = 0.29; p2 = 0.21; p3 = 0.79; p4 = 0.43), without statistical differences between the groups, except significant difference in correlation coefficients for Ccr and 1/β₂-MG between patients with GN with and without nephrotic proteinuria (p<0.032). LMW proteins, serum CyC and β₂-MG, are as good markers of GFR as Ccr, regardless sex and age. Both of these LMW proteins are good markers of GFR in patients with GN without nephrotic proteinuria, PyN and Tx patients. In patients with GN and nephrotic proteinuria serum CyC is a better marker of GFR than β₂-MG.     

Protective effect of resveratrol on renal damage in spontaneously hypertensive rats and the related mechanisms

Objective To investigate the protective effect of resveratrol (RSV) on renal damage in spontaneously hypertensive rats (SHR) and the related mechanisms on interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1). Methods Twelve male spontaneously hypertensive rats were randomly divided into two groups: model group (SHR, n＝6）and RSV group (RSV, n＝6). Six male Wistar-Kyoto rats served as control group (WKY, n＝6). RSV (20 mg·kg-1·d-1) or vehicle were gavaged for 20 weeks. Microalbuminuria and urinary β2-microglobulin were determined by urine collection from 8:00 to 16:00 at 20th week. Scr, BUN and the renal pathological changes were measured after 20 weeks. Immunohistochemistry staining of fibronectin, collagenⅠ, IL-6 and ICAM-1 were used to analysis the changes of renal fibrosis and inflammation. Real-time PCR and Western blotting were used to measure the expression of IL-6 and ICAM-1 in kidneys. Results Compared with the control group, SHR significantly increased the level of microalbuminuria, urinary β2-microglobulin (P＜0.05), but they were diminished in RSV group (P＜0.05). The expressions of fibronectin, collagenⅠ, IL-6 and ICAM-1 by immunohistochemistry staining were augmented in SHR group, and were significantly inhibited in RSV group. Compared with the control group, the expressions of renal IL-6, ICAM-1 mRNA and protein were significantly increased in SHR group (P＜0.05), and RSV treatment significantly inhibited the up-regulation (P＜0.05). Conclusions RSV treatment can attenuate microalbuminuria, urinary β2-microglobulin and renal fibrosis in SHR rats. This renal protective effect is associated with the inhibition of IL-6, ICAM-1 expression, which suggesting that inflammation may be a potential therapeutic target of hypertensive renal damage.     

The effect of connective tissue growth factor on renal fibrosis and podocyte injury in hypertensive rats

Objective: The aim of this study was to evaluate the roles of podocalyxin (PCX) and connective tissue growth factor (CTGF) in spontaneously hypertensive rats. Methods: Spontaneously hypertensive rats (SHR) and normotensive control Wistar–Kyoto (WKY) rats were divided into groups referred to as SHR 12W, SHR 24W, WKY 12W and WKY 24W. Systolic blood pressure and 24-hour total uric protein were measured every two weeks in the respective groups. CTGF, PCX, alpha-smooth muscle actin (α-SMA) and collagen-III were evaluated via immunohistochemical staining. In addition, CTGF, PCX, and α-SMA gene expression levels were determined by analyzing mRNA levels. Results: More kidney lesions occurred alongside foot processes effacement in SHR 24W rats than in SHR 12W rats. In SHR 12W rats, blood pressure and 24-hour total uric protein level were elevated and continued to increase thereafter. In the SHR 12W and SHR 24W groups, the expression of CTGF, α-SMA and collagen-III was significantly increased. Immunohistochemical staining showed that PCX expression was significantly reduced in the SHR group and CTGF expression was increased. A significant decrease in PCX mRNA and an increase in CTGF mRNA were observed in SHR 24W rats relative to SHR 12W rats. Conclusion: Both the overexpression of CTGF and the loss of podocalyxin reflect renal damage in spontaneously hypertensive rats. CTGF and PCX may be involved in the mechanisms of podocyte injury and apoptosis induced by hypertension.     

Long-term administration of prazosin improves bladder storage function: results from a study in spontaneously hypertensive rats

Objectives: To investigate the effects of long‐term administration of the α₁‐adrenoceptor antagonist prazosin on afferent inputs from the lower urinary tract (LUT). Methods: Twenty female spontaneously hypertensive rats (SHR) were randomized to receive a 4‐week course of prazosin (0.12 mg/kg per day) or vehicle; 10 female Wistar‐Kyoto (WKY) rats were given vehicle. Prazosin or vehicle was administered via an osmotic pump. The effect of prazosin on urodynamic parameters was determined by continuous cystometry in conscious animals. After cystometry, rats were killed and c‐fos expression in the dorsal horn of the L6 spinal cord was measured by immunohistochemistry. Results: The bladder contraction interval was significantly shorter in untreated SHR compared with WKY rats (2.36 ± 0 vs 4.27 ± 0.12 min, respectively; P < 0.05) and cystometric capacity was decreased significantly in SHR compared with WKY rats. L6 spinal cord c‐Fos expression was also significantly greater in SHR than WKY rats. The administration of prazosin significantly increased the micturition interval (4.07 ± 0.58 min; P < 0.05) and bladder capacity, but it did not affect micturition pressure. In SHR, the number of c‐Fos‐positive neurons was significantly lower following the administration of prazosin compared with vehicle. Conclusions: Increased afferent input from the LUT may induce an increase in urinary frequency in SHR. Furthermore, long‐term administration of prazosin can exert inhibitory effects on afferent pathways from the LUT during the storage phase. Reductions of afferent input can result in increased bladder capacity and increased micturition interval.     

Hydrogen sulphide and tempol treatments improve the blood pressure and renal excretory responses in spontaneously hypertensive rats

Oxidative stress and suppressed H₂S production lead to increased renal vascular resistance, disturbed glomerular hemodynamics, and abnormal renal sodium and water handling, contribute to the pathogenesis and maintenance of essential hypertension in man and the spontaneously hypertensive rat. This study investigated the impact of H₂S and tempol alone and in combination on blood pressure and renal hemodynamics and excretory functions in the SHR. Groups of WKY rats or SHR (n?=?6) were treated for 4?weeks either as controls or received NaHS (SHR?+?NaHS), tempol (SHR?+?Tempol), or NaHS plus tempol (SHR?+?NaHS?+?Tempol). Metabolic studies were performed on days 0, 14, and 28, thereafter animals were anaesthetized to measure renal hemodynamics and plasma oxidative and antioxidant markers. SHR control rats had higher mean arterial blood pressure (140.0?±?2 vs. 100.0?±?3?mmHg), lower plasma and urinary H₂S, creatinine clearance, urine flow rate and urinary sodium excretion, and oxidative stress compared to WKY (all p?p?2S and tempol together resulted in greater reductions in blood pressure and normalization of kidney function compared with either compound alone.     

肝糖原贮积症肾脏并发症的临床观察

目的 观察儿童期肝糖原贮积症（GSD）的肾脏并发症.方法 回顾性分析1993年1月-2004年1月北京协和医院108例病历完整的GSD患儿的肾脏损害的临床特点、治疗和预后.年龄≤10岁73例,10岁以上35例.病例随诊时间1～10年,随诊期间给予生玉米淀粉为主的综合治疗.结果 临床诊断GSD-Ⅰ a型54例（23例进行了基因诊断）;Ⅲ型29例（5例进行了基因诊断）;分型不明的25例.16例（20.8%）尿蛋白增多,发现蛋白尿时平均年龄11.3（3～21）岁,2例15岁女孩24h尿蛋白定量已达1.3 g和3.8 g,同时伴有肾功能轻度受损.51/72例（70.8%）尿β2-MG增多,为175～10 623 mg/L.5例患儿（4.6%）出现肾结石或高尿钙症,发生时年龄17.8（11～21）岁;4/5例肾绞痛伴肉眼血尿,1/5例无症状;随诊发现镜下血尿及大量草酸钙结晶,24 h尿钙456.6 mg,B型超声证实双肾多发结石.10/17例Ccr降低（48～76.9 ml/min）;2/17例Ccr升高（156.9～1819 ml/min）.5/91例BUN升高（7.4～9.3 mol/L）;1/91例Scr升高（106.1 μmol/L）.结论 GSD的肾脏合并症在儿童期已可以见到,主要表现为尿蛋白增多（白蛋白及肾小管蛋白）和肾石症,直至肾功能不全,症状随年龄增大而逐渐出现.应加强GSD患儿肾脏并发症的随诊.     

孟鲁司特钠联合双嘧达莫对儿童过敏性紫癜肾损害的保护作用

目的探讨孟鲁司特钠联合双嘧达莫对过敏性紫癜（henoch-schonlein purpura,HSP）患儿肾损害的。肾保护作用。方法将146例尿常规检查正常的HSP患儿分为3组,对照组（A组）46例给予维生素C、芦丁等常规治疗;B组57例在A组常规治疗基础上加用孟鲁司特钠治疗;C组43例在常规治疗的基础上加用孟鲁司特钠和双嘧达莫治疗。3组分别于入院时,治疗后第1个月检测尿免疫球蛋白G（immunoglobulin,IgG）、微量白蛋白（micro-albumin,mAlb）、转铁蛋白（transferrin,TRF）、Ct1微球蛋白（a1-microglobulin,a1-MG）、p2微球蛋白（p2-microglobulin,β2-MG）和N-乙酰-β-氨基葡萄糖苷酶（N-acetyl-β-D-glucosaminidase,NAG）的含量。随访6个月;比较3组血尿和（或）蛋白尿的发生率、发病时间及临床分型。结果A组治疗前后TRF、mAlb、82-MG、NAG含量比较,差异有统计学意义（P〈0．01,P〈0．05）;B、C组治疗后第1个月IgG、mAlb、TRF、α1-MG、B2-MG和NAG均较治疗前降低,除α1-MG外,差异有统计学意义（P％0．01）;B、C组治疗后第1个月IgG、mAlb、TRF、α1-MG、B2-MG和NAG均较A组降低,除Ⅸ1-MG外,差异有统计学意义（P〈0．01）;治疗后第1个月各组间IgG、mAb、TRF、α1-MG、82-MG和NAG比较,除a1-MG外,差异有统计学意义（P〈0．01）;B、C组血尿和（或）蛋白尿的发病率、发病时间及临床分型与A组比较,差异有统计学意义（P〈0．05,P〈0．01）。结论应用孟鲁司特钠或孟鲁司特钠联合双嘧达莫治疗HSP,对HSP早期肾损害均有保护作用,可能对HSP肾损害有预防作用。孟鲁司特钠联合双嘧达莫对过敏性紫癜肾损害进行早期干预疗效优于单用孟鲁司特钠。     

连黄降浊颗粒对自发性高血压大鼠肾脏功能和结构的保护作用

目的：观察连黄降浊颗粒对自发性高血压（SHR）大鼠肾脏功能和结构的保护作用。方法：将29只SHR随机分为模型组、西药对照组（对照组）、连黄降浊颗粒低剂量组（低剂量组）、连黄降浊颗粒高剂量组（高剂量组）。分别给于相应浓度和剂量的药物灌胃12周,观察大鼠的血压、尿蛋白、肾功能和血管紧张素Ⅱ（AngⅡ）、内皮素（ET）水平以及肾组织病理改变;并用半定量方法评价肾小球硬化程度、肾小管损伤程度及肾间质纤维化程度,用ELISA测定肾皮质转化生长因子-β1（TGF-β1）的蛋白定量。结果：连黄降浊颗粒能减少SHR尿蛋白、降低血压、改善肾功能、抑制AngⅡ和ET的合成,减轻肾脏病理损害,减轻肾小球硬化、肾小管损伤及肾间质纤维化程度,抑制肾脏TGF-β1表达,其效果优于苯那普利。结论：连黄降浊颗粒具有保护SHR肾功能和减轻肾脏病理损害的作用,其机制可能与减少尿蛋白、降低血压、抑制AngⅡ和ET的合成、减轻肾小球硬化和肾间质纤维化、抑制肾脏TGF-β1表达等有关。     

Detrimental effect of dietary sodium and beneficial effect of dietary magnesium on glomerular changes in cyclosporin-A-treated spontaneously hypertensive rats

Background: Cyclosporin A (CsA) causes renal magnesium wasting, hypertension, and occasionally irreversible renal damage. We examined the effect of dietary sodium and magnesium on renal histology in spontaneously hypertensive rats (SHR) receiving CsA. Methods: Forty-six 8-week-old SHR were divided into six groups and given different dietary levels of sodium (low 0.3%, high 2.6%) and magnesium (low 0.2%, high 0.6%). Low-dose CsA )5 mg/kg/d) was given subcutaneously for 6 weeks in four groups. Systolic blood pressure, serum creatinine, degree of proteinuria, and renal tissue CsA and calcium concentrations were determined. Kidney wet weight to total body-weight ratio was calculated as an index of renal hypertrophy. Renal histological alterations were scored according to glomerular changes: 100 glomeruli were assigned for severity of change a score from 0 to 3. The number of affected glomeruli was multiplied by the damage score to obtain a damage index. Results: In the CsA-treated high-sodium diet group systolic blood pressure and glomerular damage index were increased, and renal hypertrophy was the most common. These changes were prevented by oral magnesium supplementation. The glomerular damage index correlated positively with increases in systolic blood pressure, serum creatinine, proteinuria, and renal calcium concentration. Conclusions: Dietary sodium enhanced CsA-induced functional and morphological renal changes in SHR and aggravated hypertensive renal arteriolar and glomerular lesions. Dietary magnesium supplementation protected against the deleterious effects of sodium and CsA.     

罗格列酮对高血压大鼠肾间质纤维化的影响及其机制

目的探讨罗格列酮改善高血压肾间质纤维化（RIF）的机制。方法高血压大鼠随机分为阳性对照组（2K1C组）和罗格列酮治疗组（RGL组），另设假手术组（SHAM组），比较三组大鼠的尾动脉收缩压（SBP）、尿β-微球蛋白（β2-MG）、血肌酐（SCr）、尿素氮（BUN）、肾组织纤维化半定量评分以及BMP7、CTGF的表达及肾脏病理改变。结果①治疗前，2K1C组及RGL组的SBP与尿β2-MG均较SHAM组明显增加。自第4周起，RGL组SBP和尿β2-MG较2K1C组也明显降低。②2K1C组及RGL组RIF程度较SHAM组明显加重，RGL组较2K1C组减轻。③与SHAM组比较，2K1C组及RGL组BMP-7表达减少，CTGF的表达显著增加。④RGL组较2K1C组BMP7表达升高，CTGF的表达减少。⑤BMP-7及CTGF与RIF程度分别呈负相关和正相关。结论罗格列酮可能通过上调高血压大鼠肾问质BMP-7的表达、下调CTGF的表达，发挥对肾脏的保护作用。     

尿半胱氨酸蛋白酶抑制剂C在肾损害中的临床价值

目的 探讨尿半胱氨酸蛋白酶抑制剂C（Cystatin C）、α1微球蛋白（α1-MG）、β2微球蛋白（β2-MG）和N-乙酰-β-D氨基葡萄糖苷酶（N-acetyl-beta-D-glucosa minidase,NAG）对早期肾小管损害的临床价值.方法 选择我科住院的慢性肾脏病患者182例为观察组；另设健康体检者50名为正常对照组.尿Cystatin C、α1-MG、β2-MG采用酶联免疫吸附法检测,尿NAG采用比色法检测,并对2组检测结果进行比较及统计学分析.结果 观察组尿液中各项指标的测定含量明显高于正常对照组（P＜0.05）,通过接受者操作特性曲线（receiver operating characteristic curve,ROC曲线）、诊断试验结果显示尿Cystatin C曲线下面积为0.935,95％可信区间是0.872～0.997,具有统计学差异（P＜0.05）.结论 尿Cystatin C敏感性高于尿α1-MG、β2-MG、NAG酶,可以作为早期肾小管损害的诊断指标.     

Selective deep nephron hyperfiltration in uninephrectomized spontaneously hypertensive rats

Studies were carried out to determine the effect of uninephrectomy (UNX) on single nephron hemodynamics and proteinuria in the spontaneously hypertensive rat (SHR). Four groups were studied: two-kidney SHR and normotensive WKY controls; SHR + UNX and WKY + UNX. UNX was performed at age 8 to 10 weeks. Blood pressure and protein excretion were measured periodically, and micropuncture experiments of cortical nephrons were carried out at age 32 to 40 weeks. Systolic blood pressure was not significantly different between SHR and SHR + UNX. Protein excretion increased markedly in the SHR + UNX 6 months after UNX, as compared with the other three groups. In cortical nephrons, single nephron glomerular filtration rate (SNGFR) and plasma flow entering the glomeruli (SNPF) was lower in SHR + UNX than in WKY + UNX. Glomerular hydraulic pressure (PG) during stopped flow was closely comparable in all groups, rising only 2 mm Hg after UNX. SNGFR was measured in juxtamedullary (JM) nephrons 2 months after UNX, a stage before heavy proteinuria developed. We found that JM SNGFR was approximately 50% higher in SHR + UNX than in WKY + UNX. The observations suggest that following ablation of renal mass, superficial cortical glomeruli are not exposed to excessively high pressure or flow rates in the SHR. In contrast, JM glomeruli undergo a disproportionate rise in SNGFR, presumably associated with excessively high PG and/or blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is microalbuminuria a risk factor for hypertension in children with solitary kidney?

Background

The correlations between ambulatory blood pressure measurements (ABPM) and serum cystatin C (Cys C), serum creatinine (Cr), microalbumin (MA), and β2-microglobulin (β2-MG) levels in 24 h (24-h) urine were analyzed in children with solitary kidney (SK) and compared to healthy children.

Methods

Fifty children with normal functioning SK and 25 controls were studied. The ABPM, serum Cys C, serum Cr, MA, and β2-MG levels in 24-h urine were measured in all children. Clinical symptoms and signs, laboratory results, urinary ultrasonography, voiding cystourethrography, and Dimercaptosuccinic acid (DMSA) scintigraphy results were recorded in the SK group. Four patients with Wilms’ tumor and two with renal scarring were excluded from the study.

Results

The mean ages of the SK group and controls were 9.6?±?3.6 and 9.3?±?3.3 years, respectively. The serum Cys C and Cr levels, 24-h urinary β2-MG and MA levels were similar in both groups (p?>?0.05). However, 24-h urinary MA excretion was higher in patients living with SK more than 5 years (p?=?0.01). Standard deviation scores of ABPM parameters showed no significant correlation with serum Cr, serum Cys C, MA, and β2-MG in 24-h urine of both groups.

Conclusions

Children with SK have increased 24-h urinary MA excretion in the long term, and need prolonged follow-up to detect early deterioration of renal function and to prevent end-organ damage later in life.     

Effects of sevoflurane anesthesia combined with epidural block on renal function in the elderly: comparison with isoflurane

Purpose. Renal function declines with age, but little is known about the renal effects of the inhaled anesthetic sevoflurane in the elderly. We therefore compared the renal effects of sevoflurane and isoflurane anesthesia in elderly patients. Methods. Thirteen patients aged ≥70 years undergoing gastrectomy with epidural anesthesia combined with general anesthesia were randomly assigned to receive either sevoflurane (n = 7) or isoflurane (n = 6). Dopamine (3–5 μg·kg⁻¹·min⁻¹) was administered to all patients. Blood and urine samples were collected before, during, and after anesthesia. Serum and urinary inorganic fluoride was measured, and renal function tests were performed. Results. Serum inorganic fluoride was significantly elevated in both groups. The production of inorganic fluoride was significantly greater in the sevoflurane group, but the level did not exceed 50 μmol·l⁻¹ in any patient. No abnormalities were observed in blood urea nitrogen (BUN), serum creatinine, or urine volume in either group. The albumin excretion index increased during anesthesia and decreased after anesthesia in both groups. Creatinine clearance was unchanged in the sevoflurane group but fluctuated during and after anesthesia in the isoflurane group. α₁-Microglobulin (MG), β₂-MG, and urinary N-acetyl-β-d-glucosaminidase (NAG) excretion increased up to 3 h after anesthesia, and α₁-MG and β₂-MG excretion increased on postanesthesia day 3. Conclusion. In both groups, glomerular and tubular function were transiently affected, but no abnormalities were found in routine laboratory tests, suggesting that neither isoflurane nor sevoflurane in combination with dopamine and epidural anesthesia seriously affects renal function in the elderly. Received for publication on October 23, 1998; accepted on October 27, 1999     

Interaction of endothelin with renal nerves modulates kidney function in spontaneously hypertensive rats

BACKGROUND AND METHODS: We investigated kidney function, renal endothelin-1 concentration, prepro-endothelin-1 mRNA as well as endothelin receptor A and B mRNA expression and receptor properties in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) with intact renal nerves and 7 days after renal denervation. In addition, responses of renal function to the non-selective ETA/ETB receptor blocker bosentan (10 mg/kg i.v. bolus injection) were studied. RESULTS: In SHR, renal papillary prepro-endothelin-1 mRNA expression, endothelin-1 tissue concentrations and endothelin receptor density were significantly lower than in normotensive rats. Renal denervation was associated with a decrease in papillary tissue prepro-endothelin-1 mRNA and in WKY rats also with a significant reduction in papillary endothelin-1 content without affecting ET receptor density. Bosentan did not alter renal blood flow or glomerular filtration rate but decreased urine flow rate in both intact normotensive and hypertensive rats, whereas it decreased urine sodium and potassium excretion only in intact WKY. Bosentan had no effects on renal function in renal denervated rats. CONCLUSION: Since renal papillary endothelin-1 appears to counteract the fluid and sodium retaining effects of renal nerve activity, an impaired renal endothelin-1 synthesis in SHR may contribute to excessive sodium retention and thus to the pathogenesis of hypertension in SHR.     

The effect of alfuzosin on renal resistive index,urinary electrolytes and β2 microglobulin levels and TGF β-1 levels of kidney tissue in rats with unilateral ureteropelvic junction obstruction

Background: In this study, it was aimed to determine the effects of alfuzosin on experimentally generated unilateral partial ureteropelvic junction obstruction (UPO) in rats.

Materials and methods: Thirty Long–Evans rats were randomly allocated into five groups. In control group (C), nothing was performed; in group Sham (S) only laparotomy was done; in Alfuzosin group (A) only alfuzosin was administered for two weeks (10?mg/kg/day p.o.) without any surgery; in UPO group, unilateral UP junction obstruction was produced; and in the Group UPT (ureteropelvic obstruction?+?treatment), alfuzosin was administered for two weeks (10?mg/kg/day p.o.) in addition to UPO production. Renal pelvic anteroposterior diameters were determined with ultrasonography (USG) and renal arterial resistivity indexes by color Doppler USG. Urine was collected both at the beginning and at the end of the experiment for 24?h in all the groups and at the end of the experiment, blood samples were obtained. Blood and urine electrolytes and TGF-β1, urine density, urine β₂ microglobulin levels were determined. Renal tissue samples harvested from all of the rats were histopathologically evaluated. Results were determined using one-way ANOVA t-test; p?<?0.05 was accepted as significant.

Results: Urine density in the UPT group was lower with respect to UPO group and blood electrolytes were preserved as close to normal (p?<?0.05). In the UPT group, urine TGF-β1 and blood TGF-β1, blood β₂ microglobulin levels and histopathologic damage scores were lower compared to the UPO group (p?<?0.05).

Conclusion: It is shown in this experimental unilateral partial UPO model that alfuzosin treatment prevents obstructive renal damage.     

Association of renal injury with nitric oxide deficiency in aged SHR: prevention by hypertension control with AT1 blockade

BACKGROUND: Aged spontaneously hypertensive rats (SHR) develop end-stage renal disease resembling that of uncontrolled essential hypertension in humans. Nitric oxide (NO) and angiotensin II (Ang II) play an important role in the regulation of blood pressure and the growth of vascular smooth muscle and renal mesangial cells. The relationship between renal NO system, Ang II activity and renal injury in aged SHR is not fully understood. METHODS: The 8-week-old SHR were randomized into losartan-treated (30 mg/kg/day for 55 weeks) and vehicle treated groups. The age-matched Wistar-Kyoto rats (WKY) served as controls. Renal histology and tissue expressions of endothelial and inducible NO synthases (eNOS and iNOS) and nitrotyrosine were examined at 63-weeks of age. RESULTS: Compared to the WKY group, untreated SHR showed severe hypertension, proteinuria, renal insufficiency, a twofold decrease in renal tissue eNOS and iNOS expressions and massive nitrotyrosine accumulation. This was associated with severe glomerulosclerosis, tubular atrophy and interstitial fibrosis. Losartan therapy normalized blood pressure, prevented proteinuria and renal insufficiency, abrogated the fall in renal eNOS and iNOS protein contents, mitigated renal nitrotyrosine accumulation, and prevented the histological abnormalities found in the untreated SHR. CONCLUSIONS: Aged SHR exhibit severe renal lesions with acquired NO deficiency that are prevented by hypertension control with AT1 blockade. These findings point to the possible role of NO deficiency in the pathogenesis of renal lesions in aged SHR.